Home versus hospital intravenous antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis

To compare the effectiveness of home versus hospital intravenous (IV) antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis (CF). A retrospective chart review was performed of 143 encounters for pulmonary exacerbations in 50 patients with CF. All encounters were categorized into two groups based on location of completion of antibiotic therapy: hospital group completed treatment in hospital (n = 64), home group completed treatment at home (n = 79). Percent change was calculated for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced expiratory flow rate between 25 percent and 75 percent of vital capacity (FEF(25-75%)), maximum forced expiratory flow (FEF(max)), oxygen saturation (O2 SAT), and weight. Means of percent change (PC) from the beginning to the end of IV antibiotic treatment in outcome variables were compared. Total duration of treatment was compared between the two groups. The two groups had no significant differences at baseline in all outcome variables. Treatment of exacerbations in both groups resulted in significant improvement of lung function, O2 SATS, and weight (P 相似文献   

Assessing the usefulness of outcomes measured in a cystic fibrosis treatment trial

Forced expiratory volume in 1s (FEV(1)) is the usual primary outcome variable in clinical trials in cystic fibrosis (CF). Usually, several secondary outcomes are also measured. We assessed which secondary outcomes are likely to give additional clinically useful information about treatment effects, in order to inform the design of future studies. The study was performed as part of a trial comparing daily rhDNase with alternate day rhDNase and hypertonic saline in CF. The primary outcome was FEV(1). Secondary outcomes were forced vital capacity (FVC), forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75)), number of pulmonary exacerbations, weight gain, quality of life (QOL), and exercise tolerance. The usefulness of each secondary outcome was investigated by assessing if the change in that outcome over the treatment period could be predicted from the primary outcome. Change in FEV(1) correlated with changes in FVC (r(2)=0.76, P=0.001), FEF(25-75) (r(2)=0.64, P=0.001), weight (r(2)=0.08, P=0.001), and change in oxygen saturation with exercise (r(2)=0.08, P=0.001). However, it did not correlate with changes in visual analogue score (VAS) with exercise, QOL, nor with the occurrence of pulmonary exacerbations. Only the outcomes QOL and VAS with exercise actually provided additional information to FEV(1) in this study.     

Changes in lung function measured by spirometry and the forced oscillation technique in cystic fibrosis patients undergoing treatment for respiratory tract exacerbation

Objective measures of lung function are critical for the treatment and study of lung diseases such as cystic fibrosis (CF). Spirometry is the most widely used and accepted method of pulmonary function testing in CF, but not all patients can perform the maneuvers required to obtain valid results from spirometry. The forced oscillation technique (FOT) requires less cooperation than spirometry. The goals of this study were to determine if FOT could detect changes in lung function in CF patients receiving inpatient treatment of respiratory tract exacerbations (RTEs), and to gather preliminary data on the magnitude of these changes and the variability of FOT data in such patients. We performed a retrospective chart review of CF patients admitted to the hospital for RTEs. We identified 14 patients who had both spirometry and FOT performed at the beginning and end of their treatment course. Their mean age was 15.9 years (range, 8-18). The mean forced expiratory volume in 1 sec (FEV1) on admission was 62.57% predicted. FEV1 increased by 27.1 +/- 33.15% (mean +/- SD, P = 0.008). The absolute value of reactance at 5 Hz (X5) decreased by 22.3 +/- 25.1% (P = 0.005), while resistance at 5 Hz decreased by 11.6 +/- 17.3% (P = 0.025). There was a significant relationship between changes in FEV1 and X5 (P = 0.003, r2 = 0.54). Our study demonstrates that FOT can detect significant changes in lung function in CF patients receiving treatment for RTEs. We speculate that FOT can serve as an alternative method to measure lung function in CF patients unable to perform spirometry, such as young children.     

Effect of pulmonary exacerbations on long-term lung function decline in cystic fibrosis

It is unknown what proportion of long-term lung function decline in cystic fibrosis (CF) is explained by pulmonary exacerbations. The aim of this study was to determine how exacerbations requiring hospitalisation contribute to the course of CF lung disease. This was a retrospective cohort study. The primary outcome was the rate of decline of forced expiratory volume in 1 s (FEV(1)) % predicted. Out of 851 subjects, 415 (48.8%) subjects had ≥ 1 exacerbation. After adjustment for confounders, the annual rate of FEV(1) decline in those without an exacerbation was 1.2% per yr (95% CI 1.0-1.5), compared with 2.5% per yr (95% CI 2.1-2.8) in those with an exacerbation. The proportion of overall FEV(1) decline associated with ≥ 1 exacerbation was 52% (95% CI 35.0-68.9). For a given number of exacerbations, the annual rate of FEV(1) decline was greatest in subjects with ≤ 6 months between exacerbations. Half of FEV(1) decline seen in CF patients was associated with pulmonary exacerbations. Time between exacerbations, specifically ≤ 6 months between exacerbations, plays an important contribution to overall lung function decline. These findings support using time to next exacerbation as a clinical end-point for CF trials.     

Changes in spirometry during consecutive admissions for infective pulmonary exacerbations in adolescent and adult cystic fibrosis.

Changes in spirometry during consecutive admissions for treatment of pulmonary infective exacerbations were studied in 45 patients (24 males, 21 females) with cystic fibrosis (CF) who had required five or more such admissions. Over the overall study period there was a mean (SD) decline in FEV1 of -112.1 (188.0) ml yr-1 (P less than 0.001) and in FVC of -47.9 (82.4) ml yr-1 (P less than 0.001). FEV1 and FVC increased during each admission with treatment; however, the magnitude of this change became less over consecutive admissions by a mean value of -33.3 ml (45.0) (P less than 0.001) for FEV1, and -26.0 (72.2) ml (P less than 0.05) for FVC. In the majority of patients that died or underwent transplantation, FEV1 at the time of the last admission did not rise above 800 ml despite full treatment.     

The role of nebulised budesonide in the treatment of exacerbations of COPD.

The present study was designed to evaluate the hypothesis that nebulised budesonide (NB) might be an alternative to systemic corticosteroids (SC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (ECOPD). Patients hospitalised with ECOPD (n = 159) were randomised into three groups. Group 1 received only standard bronchodilator treatment (SBDT), group 2 received SC (40 mg prednisolone) plus SBDT, and group 3 received NB (1,500 microg q.i.d.) plus SBDT. Improvement during 10-day hospitalisation was compared with exacerbation and rehospitalisation rates after discharge. While mean+/-sd age was 64.1+/-8.9 yrs (female/male = 0.1), mean forced expiratory volume in one second (FEV(1)) at admission was found to be 37.2+/-12.2% predicted. Arterial blood gases and spirograms recovered faster in groups 2 and 3. While improvements in arterial oxygen tension (P(a,O(2))) and forced vital capacity (FVC) in group 2, and improvements in P(a,O(2)), FVC and FEV(1) in group 3, became significant at 24-h control, the first significant improvement in group 1 appeared in arterial oxygen saturation at 72-h control. The mean improvement of P(a,O(2)) after 10 days was 1.20 and 1.06 kPa (9 and 8 mmHg) higher in group 2 and 3, respectively, than in group 1. Blood glucose exhibited an upward trend only in group 2. The study demonstrates that nebulised budesonide may be an effective and safe alternative to systemic corticosteroids in the treatment of exacerbations of chronic obstructive pulmonary disease.     

Comparison of nebulized and intravenous terbutaline during exacerbations of pulmonary infection in patients with cystic fibrosis.

Twenty three patients completed a double-blind study, comparing intravenous and nebulized terbutaline, during the first four days of a pulmonary exacerbation of cystic fibrosis (CF), with follow-up to day 10. Routine treatment with chest physiotherapy and appropriate intravenous antibiotics was given to all patients. The best peak flow rate (PF), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), in the past year and at entry to the study, revealed no significant difference between the groups. However, on day 10, PF, FEV1 and FVC, of the nebulizer group remained significantly reduced compared to best values in the previous year, whereas the PF and FEV1 in the intravenous group were not significantly reduced compared to the best values in the previous year. Comparison of regression lines showing the overall rate of improvement of PF, FEV1 and FVC between the two groups showed that the rate of improvement of each parameter was more rapid in the group receiving intravenous terbutaline. This was statistically significant for PF. It is possible that during acute exacerbations of infection, sputum retention makes it more difficult for the inhaled bronchodilators to reach the airways and intravenous therapy is, therefore, more beneficial.     

Clinical correlations and pulmonary function at 8 years of age after severe neonatal respiratory failure

OBJECTIVES: The aim of this study was to determine the pulmonary sequelae of severe neonatal respiratory failure. STUDY DESIGN: This was a multicenter, prospective study. Fifty-four survivors of neonatal respiratory failure (oxygenation indices >25 on two occasions), completed pulmonary function testing at 8 years of age. Thirty-one (57%) received extracorporeal membrane oxygenation (ECMO). Pulmonary outcome was based on spirometry and lung volume data. Pulmonary outcome for each diagnostic and treatment group is reported as mean and as percent predicted. Individually subjects were also classified based on spirometry, as either normal, obstructed (defined as forced expiratory volume (FEV(1)) in 1 sec:forced vital capacity (FVC) of <80 % predicted, or with reduced FVC (FCV of <80% predicted) with normal FEV(1)/FVC. Risk for adverse outcome was determined using univariate analysis. RESULTS: Mean FVC, FEV(1) and FEV(25-75) were reduced in the total cohort. The reduction was greatest in the subgroup with CDH and the group treated with ECMO. Assessed individually, 54% of subjects had normal spirometry and lung volumes, 19% airflow obstruction, and 27% reduced FVC. Poorer pulmonary outcome was linked to ECMO, congenital diaphragmatic hernia (CDH), birth weight for gestational age <10th percentile, duration of hospitalization, or need for prolonged supplemental oxygen. CONCLUSION: Neonates with severe respiratory failure due to CDH or needing ECMO and small for gestation are at increased risk of poorer pulmonary outcome and require close follow-up.     

Spirometry in early childhood in cystic fibrosis patients

BACKGROUND: Spirometry data in cystic fibrosis (CF) patients in early childhood is scarce, and the ability of spirometry to detect airways obstruction is debatable. OBJECTIVE: To evaluate the ability of spirometry to detect airflow obstruction in CF patients in early childhood. METHODS: CF children (age range, 2.5 to 6.9 years) in stable clinical condition were recruited from five CF centers. The children performed guided spirometry (SpiroGame; patented by Dr. Vilzone, 2003). Spirometry indices were compared to values of a healthy early childhood population, and were analyzed with relation to age, gender, and clinical parameters (genotype, pancreatic status, and presence of Pseudomonas in sputum or oropharyngeal cultures). RESULTS: Seventy-six of 93 children tested performed acceptable spirometry. FVC, FEV1, forced expiratory flow in 0.5 s (FEV0.5), and forced expiratory flow at 50% of vital capacity (FEF50) were significantly lower than healthy (z scores, mean +/- SD: - 0.36 +/- 0.58, - 0.36 +/- 0.72, - 1.20 +/- 0.87; and - 1.80 +/- 1.47, respectively; p < 0.01); z scores for FEV1 and FVC were similar over the age ranges studied. However, z scores for FEV0.5 and forced expiratory flow at 25 to 75% of vital capacity were significantly lower in older children compared to younger children (p < 0.001), and a higher proportion of 6-year-old than 3-year-old children had z scores that were > 2 SDs below the mean (65% vs 5%, p < 0.03). Girls demonstrated lower FEF50 than boys (z scores: - 2.42 +/- 1.91 vs - 1.56 +/- 1.23; p < 0.001). Clinical parameters evaluated were not found to influence spirometric indices. CONCLUSIONS: Spirometry elicited by CF patients in early childhood can serve as an important noninvasive tool for monitoring pulmonary status. FEV0.5 and flow-related volumes might be more sensitive than the traditional FEV1 in detecting and portraying changes in lung function during early childhood.     

Cytokine levels in sputum of cystic fibrosis patients before and after antibiotic therapy

It is not known whether cytokine levels in sputum may be used as outcome measures after parenteral antibiotic therapy in cystic fibrosis (CF) patients. Here, we assessed the effects of antibiotic therapy on cytokine levels in sputum and serum obtained from young CF patients. Thirty-two CF patients (14 females; mean age, 18.6 years; range, 11.4-35.7 years), consecutively admitted at the CF Center of Milan for parenteral antibiotic therapy during pulmonary exacerbation, were enrolled in the study. Before and after 21 days (range, 5-41) of intravenous antibiotic treatment, all patients underwent routine laboratory determinations (including white blood cell (WBC) count and C-reactive protein (CRP)), a chest X-ray, pulmonary function tests (forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) as % predicted), and sputum cultures. Interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha levels in serum and sputum samples were determined by means of immunometric assays. After therapy, FEV1 and FVC significantly improved (median increase of 7.5% and 8.5% predicted, respectively), while CRP and WBC count were significantly decreased (median values from 14 to 5.5 mg/dl and from 8,350 to 7,400 n/mm3, respectively). While levels of IL-6 and IL-10 in sputum were generally undetectable, IL-8 and TNF-alpha were always measurable, and IL-8 levels significantly decreased after antibiotic treatment (median values from 7,165 to 5,415 pg/ml). Following antibiotic therapy, IL-8 and TNF-alpha levels in sputum were inversely related with both FEV(1) and FVC. In conclusion, TNF-alpha and IL-8 levels in sputum of young CF patients with pulmonary exacerbation were always detectable and may be useful, noninvasive outcome measures to assess response to therapy in CF patients.     

Does lithium carbonate affect the ion transport abnormality in cystic fibrosis?

Lithium is known to affect several aspects of cellular regulation which may be related to ion channel function in epithelial cells. To determine whether the ion transport abnormality in cystic fibrosis (CF) is affected by lithium with resultant changes in clinical status, 36 CF patients, 12-37 years old, were enrolled in a 14 week, double-blind, placebo-controlled trial. Eighteen patients were randomly assigned to receive lithium carbonate for 10 weeks. At the end of therapy their average serum lithium concentration was 0.56 +/- 0.06 mmol (SEM) per liter. Their sweat chloride concentration fell from 92.1 +/- 4.8 mmol per liter to 87.4 +/- 4.0 mmol per liter after 10 weeks of therapy (P = 0.07) and rose to 94.4 +/- 3.5 mmol per liter 4 weeks after end of therapy (P less than 0.001 compared to results at end of therapy). Their forced vital capacity (FVC) fell from 72 +/- 5.3% of predicted to 66 +/- 5.1% of predicted after 4 weeks of therapy (P less than 0.01), and their forced expiratory volume in one second (FEV1) fell from 56 +/- 5.5% of predicted to 51 +/- 5.5% of predicted after 4 weeks of therapy (P less than 0.01). In a non-blind assessment, performed 19 weeks after the end of therapy, their FVC and FEV1 had risen and were not significantly different from baseline. Sweat chloride, FVC, and FEV1 remained unchanged in the placebo group throughout the period of study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux

AIM: To study the effect of combined omeprazole (Ome) and domperidone (Dom) therapy on asthma symptoms and pulmonary function in asthmatics with gastroesoph- ageal reflux. METHODS: We selected 198 asthmatics with gastroesophageal reflux diagnosed by 24-h esophageal pH monitoring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk (1:1 double-blind randomization). Spirometry was done at baseline and af- ter 16 wk of treatment. The primary outcome measures were: mean daily daytime and nighttime asthma symp- tom scores. Mean daily reflux symptom scores, albuterol use as rescue medication (number of puffs), daytime and nighttime peak expiratory flow rate (PEFR), postbroncho- dilator forced expiratory volume in 1 second (FEV1) and postbronchodilator forced vital capacity (FVC) were secondary outcome measures. RESULTS: Comparison of mean change from baseline between antireflux therapy and placebo groups revealed significant reduction in daytime asthma symptom score (17.4% vs 8.9%), nighttime asthma symptom score (19.6% vs 5.4%), reflux symptom score (8.7% vs 1.6%) and rescue medication use (23.2% vs 3.1%) after antire- flux therapy compared to mean change in placebo group (P < 0.001). There was significant improvement in morn- ing PEFR (7.9% vs 0.2%), evening PEFR (9.8% vs 0.5%), FEV1 (11.1% vs 3.78%) and FVC (9.3% vs 1.52%) in the antireflux therapy group compared to placebo on compar-ing the mean change from baseline after 16 wk (P < 0.01).     

Predicting inadequate spirometry technique and the use of FEV1/FEV3 as an alternative to FEV1/FVC for patients with mild cognitive impairment

Introduction and Objectives: Some patients cannot perform forced vital capacity (FVC). We conducted a study to answer three questions: Can the ability to perform components of spirometry be predicted by the Mini Mental State Examination (MMSE)? What proportion of subjects can perform forced expiratory volume in 3 s (FEV3) but not FVC? Does the forced expiratory volume in 1 s (FEV1)/FEV3 ratio concord with FEV1/FVC ratio in patients with airflow obstruction? Methods: We conducted a prospective observational study of 267 patients with a mean age of 79 years, including subjects with indicators of frailty. They performed spirometry and the MMSE. Spirometric recordings were compared to the American Thoracic Society 1994 criteria. Results: FVC was achieved by 51% of patients. Inability to perform FVC was predicted by an MMSE < 24 (specificity 94%, sensitivity of 51%). An FEV1/FEV3 ratio < 80% matched a FEV1/FVC ratio < 70% (sensitivity 96%, specificity 97%). Twenty‐five percent of subjects were able to reach FEV3 but not FVC; 14% of that group had an MMSE < 24. Subjects with an MMSE < 20 were unable reliably to perform any spirometry. Conclusion: Patients with an MMSE < 24 are usually unable to reach FVC reliably when tested on a single occasion, but some can reach FEV3. Patients with MMSE < 20 cannot do spirometry. An FEV1/FEV3 ratio < 80% can be used to help identify patients with airflow obstruction if they are unable to perform full spirometry to FVC. Please cite this paper as: Allen S, Yeung P, Janczewski M and Siddique N. Predicting inadequate spirometry technique and the use of FEV1/FEV3 as an alternative to FEV1/FVC for patients with mild cognitive impairment. The Clinical Respiratory Journal 2008; 2: 208–213.     

Relationship between sputum inflammatory markers,lung function,and lung pathology on high-resolution computed tomography in children with cystic fibrosis

High-resolution computed tomography (HRCT) is a sensitive technique for early visualisation and location of cystic fibrosis (CF) bronchopathology, and has been shown to detect acute reversible and chronic changes. It would be expected to correlate with markers of the underlying pathological processes, such as sputum cytokines and cytology, as well as with pulmonary function tests (PFTs). Our aim was to study the relationship between PFTs, sputum cytology, and sputum cytokine interleukin-8 (IL-8) and HRCT in CF patients. Prospective standardized collection of sputum samples was performed at the time of routine annual high-resolution CT scans. Forced expired volume in 1 sec (FEV(1)) and forced vital capacity (FVC) were recorded. Sputum processing was selective, with dispersal by the three-enzyme technique. IL-8 measurements were by kit assay. HRCT scans were scored by a pediatric radiologist, blinded to clinical condition, using a modified Bhalla score.Forty-three CT scans were performed on 34 children with CF between March 1998 and April 2000. Mean age was 12.3 years (range, 6-21 years), FEV(1) (% predicted) was 67% (range, 23-120%), and mean modified Bhalla score was 11.2 (range, 0-22). Sputum IL-8 concentration (mean, 86; range, 4-150 ng/mL) and total cell count (mean, 31.9 x 10(6)/mL; range, 21.8-42.0 x 10(6)/mL) were high. FEV(1) and FVC correlated with modified Bhalla score (r = -0.66, P < 0.0001 for both), and most individual components of the score, especially mosaic perfusion (r = -0.64, r = -0.61 respectively, P < 0.0001) and extent of bronchiectasis (r = -0.61, P < 0.0001 for both). The combination of these two predicted 58% of the variability in FEV(1) on analysis of variance (P < 0.0001). Sputum total cell count correlated weakly with modified Bhalla score (r = 0.38, P < 0.05) and with FEV(1) and FVC (r = -0.36, P < 0.05; and r = -0.46, P < 0.01). Differential cell counts, cell viability, and IL-8 did not correlate with modified Bhalla scores, or with reversible components such as mucus plugging, centrilobular nodules, or peribronchial thickening.In conclusion, pathological changes on HRCT correlated with lung function but not with sputum markers of inflammation.     

Spirometry in children aged 3 to 5 years: reliability of forced expiratory maneuvers.

The aim of this study was to evaluate the feasibility and reproducibility of forced expiratory maneuvers during standard spirometric evaluation in preschool children. Among 570 young children attending our laboratory, we retrospectively selected 355 patients (14% 3-4-year-olds, 48% 4-5-year-olds, and 38% 5-6-year-olds) who carried out spirometric tests for the first time. The indications for such tests were history of asthma (70%), followed by chronic cough (20%) and other miscellaneous conditions (10%). Eighty-eight, 175, and 92 children performed one, two, and three acceptable tests respectively. Forced expired volume in 1 sec (FEV(1)) and forced vital capacity (FVC) did not differ significantly between attempts in children performing either two or three attempts. Forced expiratory time (FET), i.e., the total time required for the forced expiratory maneuver, was 1.7 +/- 0.1 sec (mean +/- SEM), and was no greater than 1 sec in 21.3% of all tested children. Consequently, FEV(1) does not appear to be well-suited to this age group. Forced expiratory volume in 0.50 and 0.75 sec (FEV(0.5), FEV(0.75)) were thus measured in the group of children performing three attempts (n = 92), and there was no statistical difference between attempts. In 267 children performing two or three tests, the ATS criteria of reproducing FEV(1) and FVC within 相似文献   

Annual lung function changes in young patients with chronic lung disease.

Reference equations for ventilatory function that use different statistical models may introduce artifacts that affect the estimated change of lung function during growth in young subjects. The effect of differently modelled reference equations on the estimated annual change of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in young patients with chronic lung disease was assessed. Four frequently used reference equations were used to describe the longitudinal changes of FEV1 and FVC in 52 patients (23 females) with cystic fibrosis (CF) during a mean follow-up of 3.9 yrs. Choice of reference equations directly affected value and, most importantly, estimated annual change of FVC and FEV1. Mean+/-SD annual change of FEV1 varied from 2.2+/-6.2 to -2.2+/-3.6% of predicted. For two reference equations the estimated individual changes of FEV1 and FVC in CF were positively correlated with mean individual age. This probably reflects underestimation of deteriorating lung function. Variability of annual change was independent of age only when reference equations that were designed to accurately predict lung function during the pubertal growth spurt were used. These findings have implications for patient care and clinical research.     

A comparison of spirometric values with subjects in standing and sitting positions.

Spirograms obtained from 235 subjects in standing and sitting positions revealed small differences for the forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). No statistically significant differences were found for the mean forced expiratory flow during the middle half of the FVC (FEF25-75%, or maximal midexpiratory flow) and FEV1/FVC. Sitting values were, on the average, higher for determinations greater than FVC of 2.14 L, FEV1 of 1.68 L, FEF25-75% of 2.16 L/sec, and FEV1/FVC of 75.7 percent. On the average, subjects with less than these values performed slightly better in the standing position.     

家庭无创正压通气在重度慢性阻塞性肺疾病缓解期患者中的应用价值

目的 比较长期家庭无创正压通气与长期家庭氧疗治疗缓解期重度慢性阻塞性肺疾病患者的疗效.方法 80例重度慢性阻塞性肺疾病缓解期患者分为无创正压机械通气治疗组(32例)和对照组(48例).随访2年,比较2组患者病情恶化次数、住院时间及病死率、血气分析结果、肺功能及6分钟行走距离(6MWD)、观察治疗后患者症状(咳嗽、咯痰、...     

Efficacy of once-daily tobramycin monotherapy for acute pulmonary exacerbations of cystic fibrosis: a preliminary study

Our objective was to compare the efficacy, safety, and microbiology of once-daily intravenous (IV) tobramycin with conventional 8-hourly tobramycin/ceftazidime IV therapy for acute Pseudomonas aeruginosa (PA) pulmonary exacerbations in cystic fibrosis (CF). CF patients with PA-induced pulmonary exacerbations were allocated to receive either once-daily tobramycin (Mono) or conventional therapy with tobramycin/ceftazidime given 8-hourly (Conv). The two longitudinal groups received therapy in a double-blind, randomized manner over a period of 2 years. Tobramycin doses were adjusted to achieve a daily area under the time-concentration curve of 100 mg x hr/L in both groups. Results were assessed for both short-term changes (efficacy and safety after 10 days of IV antibiotics during acute exacerbations) and long-term changes (efficacy, safety, and sputum microbiology between study entry and exit). Pulmonary function tests (PFTs) on admission were similar in both groups. After 10 days of IV antibiotics, absolute mean improvements in percent of predicted PFTs were 12.8, 12.1, and 13.7 for forced expiratory volume in 1 sec (FEV(1)), forced vital capacity (FVC), and forced expired flow between 25--75% of FVC (FEF(25--75%)) in the Conv group (n = 51 admissions) compared to 10.6, 9.9, and 10.6 in the Mono group (n = 47)(P<0.05 for all). Sixteen percent in the Conv group and 15% of patients in the Mono group did not respond to therapy by day 10. Long-term PFT patterns were similar for the Conv and Mono groups. The time between admissions did not differ. The Mono group showed a significant increase in tobramycin minimum inhibitory concentrations (MICs) against PA from study entry to study exit (P = 0.02, n = 27 strains); this failed to reach significance in the Conv group (P = 0.08, n = 25). There was no significant increase in the number of isolates, with MIC> or =8 mg/L in both groups. No short- or long-term changes in audiology or serum creatinine were found in either group. After 10 days of IV therapy, the urinary enzyme N-acetyl-beta-d-glucosaminidase/creatinine ratios increased in both groups (P0.05). This increase was greater in the Conv compared to the Mono group (P < 0.05). We conclude that this pilot study indicates once-daily tobramycin therapy to be as effective and safe as conventional 8-hourly tobramycin/ceftazidime therapy. Combination antibacterial therapy appears to offer no clinical advantage over once-daily tobramycin monotherapy. Tobramycin once-daily monotherapy is a potential alternative to conventional IV antibacterial therapy which deserves further investigation, including the impact on susceptibility of PA to tobramycin.     

Role of forced expiratory flow at 25-75% as an early marker of small airways impairment in subjects with allergic rhinitis.

A close link exists between allergic rhinitis and asthma. Small airway disease (SAD), defined by a reduction in forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75) and normal spirometry (normal forced expiratory volume at 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC ratio), may be a marker for early allergic or inflammatory involvement of the small airways in subjects with allergic diseases and no asthma. The aim of this study was to determine if there is a relationship between SAD, the outcome variable, and several allergic predictors in patients without asthma but with allergic rhinitis. A cross-sectional study was performed. Two hundred eleven midshipmen attending the third and fifth course of the Navy Academy of Livorno were screened. Fifty-eight midshipmen showed slight spirometric anomalies. Thus, they were referred to the Navy Hospital of La Spezia for standardized tests: skin-prick test, nasal cytology, spirometry, and methacholine bronchial challenge. A reduced FEF(25-75) was arbitrarily defined as < 80% of predicted. All 58 subjects had a normal FEV1, FVC, and FEV1/FVC ratio. Twenty subjects had a reduced FEF(25-75), consistent with the definition of SAD. A mean value of FEF(25-75) of 70.3 (SD, 8.5) was measured in patients with a reduced FEF, and it was 108.0 (SD, 14.3) in patients with preserved FEF(25-75). All the candidate allergic predictors appeared to be strongly associated with a reduced FEF(25-75). The proportion of subjects with reduced FEF(25-75) appeared to increase with increasing severity of the allergic predictors, and, correspondingly, the mean value of FEF(25-75) appeared to decrease. This study provides evidence that there is a relationship between SAD and allergic parameters such as nasal symptoms and eosinophils.